Induction of cell apoptosis has been a popular strategy for cancer therapy. However, selectively inducing cancer cells to die remains a big concern and challenge for cancer theatment.
Mechanism studies showed that NPP induces apoptosis by cytochrome P450-catalyzed reactive oxygen species (ROS) formation. Using NPP as a tool, researchers explored the susceptibility of tumor cells to ROS-induced cell death.
The results suggest that high basal ROS levels, low antioxidant capacities and loss of p53 in tumor cells increase their sensitivity to the ROS inducers. Additionally, the comparison of NPP to other ROS inducers shows that the cytotoxic effects of ROS inducers are influenced by the mode, the amount, the duration, and perhaps the location of the ROS production.
This work not only provides a unique anti-cancer drug candidate, but also sheds new light on the understanding of ROS generation and function, and the potential application of ROS-promoting strategy in cancer treatment. This work has been formally published on the Journal of Biological Chemistry (March 29, 2013, 288: 8826-8837).
This work was supported by the China Ministry of Science&Technology “Key New Drug Creation and Manufacturing Program”, the China Ministry of Science and Technology Research Grant, the China National Natural Science Foundation Grants, and the National Science and Technology 973 grants.
Model of the mechanism of NPP (Image by SIMM)
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